Nonuniform behavior of intravenous anesthetics on postischemic adhesion ofneutrophils in the guinea pig heart

Adhesion of polymorphonuclear neutrophils (PMN) to the coronary endothelium is a crucial step in the development of ischemic myocardial injury. We tes ted the possible effects of six widely used IV anesthetics on non- and post ischemic coronary adhesion of PMN in isolated perfused guinea pig hearts. H earts (n = 5-11/group) were perfused under conditions of constant coronary flow. After 15 min global warm ischemia, PMN (10(6)) were infused in the se cond minute of reperfusion. The number of cells reemerging in the coronary effluent within 2 min was expressed as a percentage of the total number of administered PMN. Anesthetics were given 20 min before ischemia and during reperfusion. In addition, the ability of the drugs to influence the oxidati ve burst reaction of PMN was assessed by measuring luminol-enhanced chemilu minescence in response to 0.1 mu M N-formyl-L-methionyl-L-leucyl-L-phenylal anine. Under nonischemic conditions, 26.3% +/- 0.5% of the injected PMN did not acutely reemerge from the coronary system. Subjecting the hearts to is chemia augmented retention to 40.0% +/- 1.6% (P < 0.05). This postischemic stimulation of adhesion was fully prevented by ketamine (10 mu M: 22.8% +/- 1.6%, 20 mu M: 26.6% +/- 0.7%), thiopental (25 mu M: 24.0% +/- 1.7%, 50 mu M: 24.0% +/- 1.4%), and midazolam (1.5 mu M: 29.0% +/- 0.9%, 3 mu M: 26.4% +/- 1.4%). Propofol also inhibited the augmented postischemic retention at 25 mu M (28.7% +/- 2.4%). However, 50 mu M propofol, etomidate (0.5 and 1 mu M), and fentanyl (1 mu M) all had no effect. Only thiopental reduced the nonischemic adhesion value (14.0% +/- 3.7%). This may be linked to the dir ect antioxidative action of thiopental (50% reduction in oxidative burst ac tivity). Whereas ketamine, midazolam, and propofol did not significantly in fluence oxidant production by PMN, etomidate and the lipid solvent Intralip id enhanced the burst reaction. This activating effect of the lipid compone nt could explain the biphasic behavior of propofol emulsion. Despite some p ossible differences in efficacy, several IV anesthetics may protect the hea rt from PMN-mediated reperfusion injury.